ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.76G>T (p.Glu26Ter)

dbSNP: rs786201058
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen CDH1 Variant Curation Expert Panel RCV003328245 SCV001142243 pathogenic CDH1-related diffuse gastric and lobular breast cancer syndrome 2023-08-04 reviewed by expert panel curation The c.76G>T p.(Glu26Ter) variant is predicted to result in a premature stop codon that leads to nonsense mediate decay (PVS1 and PM5_supporting). The variant is absent in the gnomAD cohort (PM2_supporting; http://gnomad.broadinstitute.org). Therefore, this variant meets criteria to be classified as pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (CDH1 VCEP specifications version 3.1): PVS1, PM2_supporting, PM5_supporting.
Ambry Genetics RCV000162463 SCV000212823 pathogenic Hereditary cancer-predisposing syndrome 2014-12-02 criteria provided, single submitter clinical testing The p.E26* pathogenic mutation (also known as c.76G>T), located in coding exon 2 of the CDH1 gene, results from a G to T substitution at nucleotide position 76. This changes the amino acid from a glutamic acid to a stop codon within coding exon 2. Since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Invitae RCV000797095 SCV000936635 pathogenic Hereditary diffuse gastric adenocarcinoma 2023-01-19 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 183750). This premature translational stop signal has been observed in individual(s) with Breast Cancer (PMID: 31263571). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu26*) in the CDH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CDH1 are known to be pathogenic (PMID: 15235021, 20373070).
Myriad Genetics, Inc. RCV000797095 SCV004044059 pathogenic Hereditary diffuse gastric adenocarcinoma 2023-06-08 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.

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